Comparison of Helix-Stabilizing Effects of \alpha, \alpha - Dialkyl Glycines with Linear and Cycloalkyl Side Chains

Vijayalakshmi, S and Rao, Balaji R and Karle, IL and Balaram, P (2000) Comparison of Helix-Stabilizing Effects of \alpha, \alpha - Dialkyl Glycines with Linear and Cycloalkyl Side Chains. In: Biopolymers, 53 (1). pp. 84-98.

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Abstract

The ability of \alpha, \alpha -di-n-alkyl glycines with linear and cyclic alkyl side chains to stabilize helical conformations has been compared using a model heptapeptide sequence. The conformations of five synthetic heptapeptides (Boc–Val–Ala–Leu–Xxx–Val–Ala–Leu–OMe, $Xxx = Ac_8c, Ac_7c, Aib, Dpg ,and Deg, where Ac_8c$ = 1-aminocyclooctane-1-carboxylic acid, $Ac_7c$ = 1-aminocycloheptane-1-carboxylic acid, Aib = a-aminoisobutyric acid, Dpg = \alpha, \alpha -di-n-propyl glycine, Deg = \alpha, \alpha -din- ethyl glycine) have been investigated. In crystals, helical conformations have been demonstrated by x-ray crystallography for the peptides, R–Val–Ala–Leu–Dpg–Val–Ala–Leu–OMe, (R = Boc and acetyl). Solution conformations of the five peptides have been studied by $^1H-nmr$. In the apolar solvent $CDCl_3$, all five peptides favor helical conformations in which the NH groups of residues 3–7 are shielded from the solvent. Successive $N_iH \leftrightarrow N_{i+1}H$ nuclear Overhauser effects over the length of the sequence support a major population of continuous helical conformations. Solvent titration experiments in mixtures of $CDCl_3/DMSO$ provide evidence for solvent-dependent conformational transitions that are more pronounced for the Deg and Dpg peptides. Solvent-dependent chemical shift variations and temperature coefficients in DMSO suggest that the conformational distributions in the Deg/Dpg peptides are distinctly different from the $Aib/Ac_nc$ peptides in a strongly solvating medium. Nuclear Overhauser effects provide additional evidence for the population of extended backbone conformations in the Dpg peptide, while a significant residual population of helical conformations is still detectable in the isomeric $Ac_7c$ peptide in DMSO.

Item Type:	Journal Article
Publication:	Biopolymers
Publisher:	John Wiley & Sons, Inc.
Additional Information:	The copyright belongs to John Wiley & Sons, Inc.
Keywords:	Heptapeptides;Alpha-helix;310 helix;Crystal structures;Solution structures;Helix transitions;Solvent dependency
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	20 Mar 2006
Last Modified:	19 Sep 2010 04:24
URI:	http://eprints.iisc.ac.in/id/eprint/5630

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